The presence of bacteria in human milk has been acknowledged since the seventies. For a long time, microbiological analysis of human milk was only performed in case of infections and therefore the presence of non-pathogenic bacteria was yet unknown. During the last decades, the use of more sophisticated culture-dependent and -independent techniques, and the steady development of the -omic approaches are opening up the new concept of the 'milk microbiome', a complex ecosystem with a greater diversity than previously anticipated. In this review, possible mechanisms by which bacteria can reach the mammary gland (contamination versus active migration) are discussed. In addition, the potential roles of human milk for both infant and maternal health are summarised. A better understanding of the link between the milk microbiome and health benefit, the potential factors influencing this relationship and whether or not it can be influenced by nutrition is required to open new avenues in the field of pregnancy and lactation.
TLRs play a major role in microbe-host interactions and innate immunity. Of the 10 functional TLRs described in humans, TLR2 is unique in its requirement to form heterodimers with TLR1 or TLR6 for the initiation of signaling and cellular activation. The ligand specificity of TLR2 heterodimers has been studied extensively, using specific bacterial and synthetic lipoproteins to gain insight into the structure-function relationship, the minimal active motifs, and the critical dependence on TLR1 or TLR6 for activation. Different from that for specific well-defined TLR2 agonists, recognition of more complex ligands like intact microbes or molecules from endogenous origin requires TLR2 to interact with additional coreceptors. A breadth of data has been published on ligand-induced interactions of TLR2 with additional pattern recognition receptors such as CD14, scavenger receptors, integrins, and a range of other receptors, all of them important factors in TLR2 function. This review summarizes the roles of TLR2 in vivo and in specific immune cell types and integrates this information with a detailed review of our current understanding of the roles of specific coreceptors and ligands in regulating TLR2 functions. Understanding how these processes affect intracellular signaling and drive functional immune responses will lead to a better understanding of host-microbe interactions and will aid in the design of new agents to target TLR2 function in health and disease.
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